A kind of 4-perfluoroalkyl substituted pyrimidine compound and its preparation method and application

A perfluoroalkyl compound technology, applied in the field of 4-perfluoroalkyl substituted pyrimidine compounds and its preparation, can solve the problems of inability to synthesize perfluoroalkyl pyrimidines, limitations of compound substrates, and low yield of target products. Achieve good substrate universality, good functional group tolerance, and expand the range of prepared substrates

Active Publication Date: 2022-05-24
NANJING TECH UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But, the synthetic method of the pyrimidine compound containing perfluoroalkyl is still less, existing record mainly comprises: (1) the direct condensation of the unsaturated aldehyde that contains perfluoroalkyl, ketone and amidine compound (Eur.J .Org.2017,2017,4121-4129), but the synthesized compound substrates are very limited, and can not synthesize perfluoroalkyl pyrimidines substituted with different chain lengths; (2) from alkenes, amidines, perfluoroalkyl iodides Participated in the multi-component condensation reaction (Chem.Commun., 2018, 54, 2615-2618), but this synthesis method needs to be carried out under harsh conditions such as transition metals and strong oxidants, and more by-products, resulting in lower yields of the target product

Method used

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  • A kind of 4-perfluoroalkyl substituted pyrimidine compound and its preparation method and application
  • A kind of 4-perfluoroalkyl substituted pyrimidine compound and its preparation method and application
  • A kind of 4-perfluoroalkyl substituted pyrimidine compound and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] (1) Add 0.3 mmol of perfluoroalkyl-substituted alkyne compound (96.0 mg), 0.36 mmol of amidine hydrochloride (56.4 mg), and 0.9 mmol of alkali accelerator (293.2 mg) to a 10 mL test tube In the reaction tube, 2 mL of N,N-dimethylacetamide was added to the reaction tube as a solvent, the seal was sealed, and the reaction was stirred at 70 degrees Celsius for 24 hours to obtain a 4-perfluoroalkyl-substituted pyrimidine compound; The base-substituted alkyne compound is (perfluorohexyl-1-yn-1-yl)benzene; the amidine hydrochloride is benzamidine hydrochloride; the base additive is cesium carbonate;

[0039] (2) after the reaction in step (1) finishes, the reaction solution is successively dried by water, ethyl acetate, anhydrous sodium sulfate and separated by column chromatography (column chromatography separation condition: the stationary phase is 300~400 mesh silica gel powder, The mobile phase was ethyl acetate (A) and petroleum ether (B), and the mobile phase change pro...

Embodiment 2～55

[0043] Examples 2 to 55 are basically the same as the above-mentioned Example 1, except that in step (1), the perfluoroalkyl-substituted alkyne compound and the amidine hydrochloride are different, as shown in Table 1 below:

[0044] Table 1 Examples 2 to 55

[0045]

[0046]

Embodiment 56～77

[0048] Embodiments 56 to 77 are basically the same as the above-mentioned embodiment 1, except that in step (1), the alkali accelerator, solvent, temperature (°C), and time (h) are different, as shown in Table 2 below:

[0049] Table 2

[0050] Example number Alkali accelerator solvent temperature(℃) time (h) Yield(%) 56 Cesium carbonate N,N-Dimethylacetamide 70 24 77 57 Pyridine N,N-Dimethylacetamide 70 24 very little 58 Triethylenediamine N,N-Dimethylacetamide 70 24 very little 59 triethylamine N,N-Dimethylacetamide 70 24 very little 60 diazabicyclo N,N-Dimethylacetamide 70 24 very little 61 sodium hydride N,N-Dimethylacetamide 70 24 23 62 Potassium carbonate N,N-Dimethylacetamide 70 24 67 63 Sodium acetate N,N-Dimethylacetamide 70 24 10 64 sodium hydroxide N,N-Dimethylacetamide 70 24 45 65 Cesium carbonate N,N-Dimethylformamide 70 24 53 66 ...

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Abstract

The invention discloses a 4-perfluoroalkyl substituted pyrimidine compound, a preparation method and application thereof. In the present invention, alkali additives and solvents are added to the reaction raw materials mixed with perfluoroalkyl substituted alkyne compounds and amidine hydrochloride, stirred and reacted for 1 to 24 hours in an air atmosphere at 70°C, and determined by TLC detection The reaction process, the reaction product is obtained after the reaction is completed, the reaction product is washed, extracted and dried, and then separated by column chromatography to obtain a 4-perfluoroalkyl substituted pyrimidine compound. The preparation method of the present invention has mild reaction conditions, does not need expensive transition metal catalysts, only uses inorganic alkali cesium carbonate as an additive, has the characteristics of simple post-treatment, green steps, low pollution, and high economic benefits, and the prepared compound is a novel multi-substituted pyrimidine molecule. It has good application prospects in the fields of new medicine and new material development.

Description

technical field [0001] The invention belongs to the fields of organic chemistry and medicinal chemistry, and in particular relates to a 4-perfluoroalkyl substituted pyrimidine compound and a preparation method and application thereof. Background technique [0002] Pyrimidine derivatives are an important class of N-containing heterocycles, and are one of the most critical molecular skeletons in many biologically active molecules and natural products. They have special applications in materials chemistry, natural products, organic synthesis and medicinal chemistry. For example, mepiperidine can be used as an antipsychotic drug; pyrimethamine can inhibit Plasmodium; Rosuvastatin is a good drug for the treatment of hypertension. In addition, Gemigliptin, a hypoglycemic drug based on the mechanism of action of incretin, jointly developed by Bristol-Myers Squibb of the United States and AstraZeneca of the United Kingdom, has been used in many countries including the United States,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/26
CPCC07D239/26
Inventor 褚雪强沈志良孙莉雯
Owner NANJING TECH UNIV
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